CYP3A4 inhibitors isolated from a marine derived fungus <Emphasis Type="Italic">Penicillium</Emphasis> species

More than 50% of clinically used drugs are thought to be metabolized by cytochrome P450 (CYP) 3A4. Discovery of new, inexpensive, CYP3A4 inhibitors will reduce drug dosages needed to cure patients. In our search for new inhibitors of the enzyme CYP3A4, extracts from 102 marine fungi were screened. Seven of the extracts had potent CYP3A4 inhibitory activity. Four aromatic compounds were isolated from an extract of a culture of one of these, a Penicillium sp., and were identified as 3-methoxyphenol (1), 4-methoxyphenylacetic acid (2), 4-(2-hydroxyethyl)phenol (3), and 4-hydroxy-2-methoxyacetanilide (4) by use of spectroscopic data. Interestingly, compound 3 at 250 μg mL⁻¹did not inhibit CYP3A4 whereas compounds 1, 2 and 4 had CYP inhibitory activity with IC₅₀ values of 2.0, 1.6 and 0.41 μg mL⁻¹, respectively.